Transferrin is a protein found in the blood of all humans and its known function is to carry iron to those organs and cells of the body that require this metal for normal function. Recently, scientists have reported that an important function of iron carried by transferrin is to control the division of body cells. E. Robbins et al. Proceedings National Acadeny Science U.S.A., 66: 1244 (1970); P. Rudland, et al., Biochemical Biophysical Research Communications, 75: 556 (1977). It has been known for some time that when a person becomes afflicted with a neoplastic growth, the quantity of iron in the blod carried by transferrin is severely diminished. M. Beamish, et al., British Journal of Cancer, 26: 444 (1972); N. Hughes, Australian Journal of Experimental Biological Medicine Science, 50: 97 (1972). The applicant of the present invention and others investigated this depletion of iron bound to transferrin in the blood of rats with malignant tumors, and found that the iron had not left the body, but instead had been relocated and accumulated in tissue containing neoplastic cells. F. Warner, R. Stjerhnolm, and I. Cohn, Medical Physics, 5: 100 (1978); N. Dodd et al., British Journal of Cancer, 34: 556 (1976). It was also observed that when the rat tumor was put into remission by a variety of anti-neoplastic drugs, the serum levels of transferrin bound iron returned to normal. These results indicated that when the tumor cells are not multiplying, iron was not concentrated in the neoplasms. F. Warner, M. de Manuelle, R. Stjernholm, I. Cohn and W. Baddley, Journal of Clinical Hemotology and Oncology, 7: 180 (1977). Other research leading to the instant patent showed that human breast carcinoma tissue contained larger quantities of transferrin bound iron than surrounding apparently normal tissue. F. Santoliguido, et al. Surgery, Gynecology and Obstretics, 142: 65 (1976); W. Faulk, Lancet, pg. 390, Aug. 23, 1980. For iron specifically bound to transferrin to play such a vital role in controlling cell division, the intracellular chemistry of cell division must be so unique that if natural transferrin bound iron is properly replaced by another metal, disruption of the cell division processes will occur.
Since platinum was already known to kill cancer cells, J. Marks, Science, 192: 774 (1976), Cancer Treatment Chemotherapy (C. Haskell, ed.) W. B. Saunders Co., pgs. 112-114 (1980); "Proceedings Third International Symposium on Platinum Coordination Complexes in Cancer Chemotherapy", Journal Clinical Hemotology & Oncology, Vols. 1 and 2 (1977), the applicant chose it as a metal to replace iron on the protein transferrin. R. Stjernholm, et al., Bioinorganic Chemistry, 9: 277 (1978). Because of its toxicity, platinum has been used in the past in organometallic moieties and compounds to treat neoplastic growths, for instance in the U.S. Pat. Nos. 4,053,587, 4,151,185, 4,169,846, 4,175,133, 4,177,263, 4,206,208, 4,234,499, 4,234,500, 4,284,579. However, these previous therapeutic agents incorporating platinum had severe drawbacks in a clinical context. Specifically, the platinum chemotherapeutic agents would not specifically attack and kill the neoplastic cells, but instead caused damage to normal cells as well. Many of the platinum compounds also activated the body's immune systems, creating further side effects and causing the foreign substances to be rapidly removed from the body, thereby reducing the therapeutic effect of the drugs. These platinum based chemotherapeutic agents can cause kidney dysfunction, hearing problems, and intestinal antagonism. J. Marks, Science, 192: 774 (1976), Cancer Treatment Chemotherapy (Haskell, ed.), W. B. Saunders Co., pgs 112-114 (1980). "Proceedings Third International Symposium on Platinum Coordination Complexes in Cancer Chemotherapy", Journal of Clinical Hematology & Oncology, Vols. 1 and 2 (1977). Under certain circumstances, kidney failure results, which in itself can be fatal. Even most of the non-metal based cancer treatments cause traumatic side effects: falling out of hair, nausea, etc.
The specific form of the platinum starting material which has been found most useful in therapeutic applications is cis-Dichlorodiammineplatinum (II). The invention is not limited to cis-Dichlorodiammineplatinum (II), since other inorganic platinum starting materials may be useful. However, most research to date in the field of oncology has focused on cis-Dichloradiammineplatinum (II) (cis-platinum)